Only few compounds are known to possess antiviral activity. One of the best is interferon, which is currently in experimental therapeutic use in humans. The production and purification of human interferon is fairly tedious and the available quantities are limited. However, much is known today about the mechanism of action of this antiviral protein which acts by inducing an antiviral state in cells (Antiviral Drugs and Interferon: The molecular Basis of their Activity. Ed Yechiel Becker 1984, p. 357, Martinus Nijhoff Publishing Boston). The active ingredient, hypericin and pseudohypericin can be isolated and purified. The results of our investigation led to the isolation from the plant Hypericum triquetrifolium Turra, also known as Hypericum crispum L., of two compounds identified chemically as hypericin (1) and pseudohypericin (2). These compounds have been isolated among others in a pure form and characterized using NMR techniques. Their spectra showed all the characteristic signals specific for their polycyclic aromatic structures. ##STR1## These two compounds showed an unequivocal and strong antiviral activity against vesicular stomatitis virus (VSV), influenza virus, herpes simplex HSV-1 and HSV-2 and others. Their toxicity was found to be low in tissue cultures and in mammals. Tests performed on the incorporation of radioactive .sup.3 H-uridine into RNA by the virus-indicated that the activity of these two compounds involves an inhibition of RNA synthesis, interfering with the replication of the virus, resulting in its destruction.
In order to display their activity, the compounds have to be in direct contact with the virus. The estimation of the antiviral activity is based on protection of cells by the compounds from destruction by the virus, previously put in contact with low concentrations of the compounds tested.
In view of this behaviour the compounds are appropriate for topical application in localized infections.
The compounds have been described earlier by Brockmann et al. (H. Brockmann and W. Sanne. Zur Kenntnis des Hypericins und Pseudo-hypericins. Chem. Ber. 90, 2480, (1957)); H. Brockmann, U. Franssen, D. Spitzner and H. Augustiniak. Zur Isolierung und Konstitution des Pseudohypericins, Tetrahedron Letters, 1991, (1974)) who have also provided the appropriate NMR signals for each of the two compounds (1) and (2) (H. Brockmann and D. Spitzner. Die Konstitution des pseudohypericins, Tetrahedron Letters 37, (1975)). A synthesis for hypericin has also been reported (H. Brockmann, F. Kluge and H. Muxfeldt. Totalsynthese des Hypericins, Chem. Ber. 90, 2302 (1957)). Although species of the genus Hypericum (St. John's wort) have been reported to display an antiviral activity (N.A. Derbentseva et al., Effect of tannins from Hypericum perforatum on influenza virus Mikrobiol. Zh. (Kiev) 34, 768 (1972) C.A. 78 67532d; Mishenkova et al., Antiviral properties of St. John's wort and preparation produced from it. Tr. S'ezda Mikrobiol. Ukr. 4th. 222 (1975), C.A. 85 187161Y), the two compounds hypericin (1) and pseudohypericin (2) have never been reported or recorded to have antiviral activity.
Hypericin (1) is also described in the Merck Index (Eighth edition, O. G. Stecher Ed., 1968, p 558) as appearing to have a tonic and tranquilizing action on the human organism. It has been used in medicine as antidepressant (Daniel K. Further communication on the photodynamic substance hypericin. Hippokrates 20, 526 (1949); C.A. 46 9721/e (1952)).